Field
The invention relates to a novel process for preparing polyfluoroalkylated quinolines from ketimines in the presence of fluoroalkylamino reagents.
Description of Related Art
Quinolines are important precursors to pharmaceuticals and agrochemicals ((a) J. Sloop, J. Phys. Org. Chem., 2009, 22, 110-117; (b) A. R. Surrey and H. F. Hammer, J. Am. Chem. Soc., 1946, 68, 113-116; (c) W. Jonhson and B. G. Buetl, J. Am. Chem. Soc., 1952, 74, 4513-4516; (d) J. Mulero, G. Martinez, J. Oliva, S. Cermeno, J. M. Cayuela, P. Zafrilla, A. Martinez-Cacha and A. Barba, Food Chem, 2015, 180, 25-31).
The Combes reaction starting from β-diketones and anilines is an important method for the synthesis of quinolines (Chem. Ber., 1896, 29, 2456). However the Combes reaction has only limited importance for the preparation of quinolines containing perfluoroalkyl groups in position 2 and 4. J. Sloop et al. (J. Fluorine Chem., 2002, 118, 135-147) described an application of the Combes synthesis using anilines and fluorinated β-diketones in polyphosphoric acid. The fluorinated β-diketones usually prepared via Claisen condensation are hardly accessible. Especially in the case of fluorinated β-diketones the yields of this reaction are rather low and the isolation of the highly volatile products is quite difficult. Moreover, a cyclization of unsymmetrical β-diketones under Combes conditions leads to the formation of regioisomers (see J. Sloop et al., J. Fluorine Chem., 2002, 118, 135-147). In addition, the isolation of quinolines from the reaction mixture containing polyphosphoric acid produces large amount of P-containing waste.